Pexiganan, a 22-amino-acid synthetic cationic
peptide, is currently in phase 3 clinical trials as a topical
antimicrobial agent for the treatment of mild
infections associated with
diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from
diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various
infection types that harbored selected resistance mechanisms/phenotypes were tested against
pexiganan in reference
cation-adjusted Mueller-Hinton broth. The MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 μg/ml, respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC values ranged from 8 to 16 μg/ml.
Pexiganan MIC values among Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and
methicillin-susceptible S. aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faecium ranged from 8 to 32 μg/ml.
Pexiganan activity was not adversely affected for members of the family Enterobacteriaceae or P. aeruginosa that produced β-lactamases or resistance mechanisms to other commonly used
antimicrobial agents. Decreased susceptibility to
vancomycin did not affect
pexiganan activity against S. aureus or E. faecium. Enterococcus faecalis appears to be intrinsically less susceptible to
pexiganan (MIC, 32 to 256 μg/ml). The "all organism" MIC90 of 32 μg/ml for
pexiganan in this study was >250-fold below the
pexiganan concentration in the cream/delivery vehicle being developed for topical use.